1. Field of the Invention
The present invention relates to novel anthracycline antibiotics having a carcinostatic activity.
2. Prior Art
As carcinostatic anthracycline antibiotics, hithereto, daunomycin (refer to U.S. Pat. No. 3,616,242) and adriamycin (refer to U.S. Pat. No. 3,590,028) are known, and these two are compounds which are most widely utilized for clinical use at present as a carcinostatic chemotherapeutical agent. However, these have serious cardiotoxic activity and myelotoxic activity, even though they have an excellent carcinostatic activity. Therefore, these are not absolutely satisfactory as carcinostatic agents. Under the circumstances, production of compounds whose harmful side effect is reduced and whose carcinostatic activity is improved is desired, and some anthracycline antibiotics have already been proposed to be produced by means of a fermentation method, microbial conversion method and chemical synthesis method. For instance, specific examples of known antibiotics include acracinomycin A and acracinomycin B (refer to JP-B No. 51-34914 - the term "JP-B" as used herein means an "examined Japanese patent publication"), rhodomycin antibiotics (refer to JP-A No. 56-15299 - the term "JP-A" as used herein means an "unexamined published Japanese patent application"), 4'-O-tetrahycoropyranyl-adriamycin (refer to JP-B No. 57-13558), 3'-deamino-3'-morpholino-daynomycin and 3'-deamino-3'-morpholino-adriamycin (refer to JP-A No. 57-163393). Other daunomycin and adriamycin derivatives are described in Topics in Antibiotics Chemistry, Vol. 12, pages 102 to 279 (published by Ellis Horwood Limited) and The Chemistry of Antitumor Antibiotics, Vol. 1, pages 63 to 132 (published by Wiley-Interscience).
As a tumoricidal agent, various kinds of analogous compounds of anthracycline antibiotics have been proposed, as mentioned above, and some of them have already been widely utilized for clinical use while some others have been put to a clinical demonstration. However, none are satisfactory in both the non-toxicity and the carcinostatic activity. In addition, in most tumoricides, the in vivo test results and animal test results are not always related directly to the carcinostatic activity of human cancers, and therefore, many-sided studies are required for tumoricidal substances. Accordingly, regarding the anthracycline carcinostatics which have been evaluated to be effective to some degree as a tumoricide, there is a desire to obtain a new group of compounds which are more effective as a clinical medicine.
The present inventors have previously illustrated methods of producing specific new anthracycline antibiotics having an excellent activity by microbial conversion of various anthracycline-aglycones with an aclacinomycin-producing strain (Streptomyces galilaeus KE 303 (FERM BP-2048). For example, refer to JP-A No. 56-15299 (rhodomycin antibiotics) and JP-A No. 57-165399 (2-hydroxyacracinomycin A).